Showing papers by "Huige Li published in 2022"

Redox Regulatory Changes of Circadian Rhythm by the Environmental Risk Factors Traffic Noise and Air Pollution

Abstract: Significance: Risk factors in the environment such as air pollution and traffic noise contribute to the development of chronic noncommunicable diseases. Recent Advances: Epidemiological data suggest that air pollution and traffic noise are associated with a higher risk for cardiovascular, metabolic, and mental disease, including hypertension, heart failure, myocardial infarction, diabetes, arrhythmia, stroke, neurodegeneration, depression, and anxiety disorders, mainly by activation of stress hormone signaling, inflammation, and oxidative stress. Critical Issues: We here provide an in-depth review on the impact of the environmental risk factors air pollution and traffic noise exposure (components of the external exposome) on cardiovascular health, with special emphasis on the role of environmentally triggered oxidative stress and dysregulation of the circadian clock. Also, a general introduction on the contribution of circadian rhythms to cardiovascular health and disease as well as a detailed mechanistic discussion of redox regulatory pathways of the circadian clock system is provided. Future Directions: Finally, we discuss the potential of preventive strategies or “chrono” therapy for cardioprotection. Antioxid. Redox Signal. 37, 679–703.

Endothelial Nitric Oxide Synthase in the Perivascular Adipose Tissue

Abstract: Perivascular adipose tissue (PVAT) is a special type of ectopic fat depot that adheres to most vasculatures. PVAT has been shown to exert anticontractile effects on the blood vessels and confers protective effects against metabolic and cardiovascular diseases. PVAT plays a critical role in vascular homeostasis via secreting adipokine, hormones, and growth factors. Endothelial nitric oxide synthase (eNOS; also known as NOS3 or NOSIII) is well-known for its role in the generation of vasoprotective nitric oxide (NO). eNOS is primarily expressed, but not exclusively, in endothelial cells, while recent studies have identified its expression in both adipocytes and endothelial cells of PVAT. PVAT eNOS is an important player in the protective role of PVAT. Different studies have demonstrated that, under obesity-linked metabolic diseases, PVAT eNOS may be even more important than endothelium eNOS in obesity-induced vascular dysfunction, which may be attributed to certain PVAT eNOS-specific functions. In this review, we summarized the current understanding of eNOS expression in PVAT, its function under both physiological and pathological conditions and listed out a few pharmacological interventions of interest that target eNOS in PVAT.

<scp>l</scp> ‐Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia

Abstract: Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with l-citrulline in Dahl salt-sensitive rats, a model of superimposed preeclampsia.Parental Dahl salt-sensitive rats were treated with l-citrulline (2.5 g·L-1 in drinking water) from the day of mating to the end of lactation period. Blood pressure was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant Dahl salt-sensitive rats was assessed by wire myograph.In Dahl salt-sensitive rats, l-citrulline supplementation significantly reduced maternal blood pressure, proteinuria and levels of circulating soluble fms-like tyrosine kinase 1. l-Citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. l-Citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, l-citrulline down-regulated genes involved in the TLR4 and NF-κB signalling pathways.This study shows that l-citrulline supplementation reduced gestational hypertension and improved placentation and fetal growth in a rat model of superimposed preeclampsia. l-Citrulline supplementation may provide an effective and safe therapeutic strategy for preeclampsia that benefits both the mother and the fetus.

Measurement of Tetrahydrobiopterin in Animal Tissue Samples by HPLC with Electrochemical Detection—Protocol Optimization and Pitfalls

Abstract: Tetrahydrobiopterin (BH4) is an essential cofactor of all nitric oxide synthase isoforms, thus determination of BH4 levels can provide important mechanistic insight into diseases. We established a protocol for high-performance liquid chromatography/electrochemical detection (HPLC/ECD)-based determination of BH4 in tissue samples. We first determined the optimal storage and work-up conditions for authentic BH4 and its oxidation product dihydrobiopterin (BH2) under various conditions (pH, temperature, presence of antioxidants, metal chelators, and storage time). We then applied optimized protocols for detection of BH4 in tissues of septic (induced by lipopolysaccharide [LPS]) rats. BH4 standards in HCl are stabilized by addition of 1,4-dithioerythritol (DTE) and diethylenetriaminepentaacetic acid (DTPA), while HCl was sufficient for BH2 standard stabilization. Overnight storage of BH4 standard solutions at room temperature in HCl without antioxidants caused complete loss of BH4 and the formation of BH2. We further optimized the protocol to separate ascorbate and the BH4 tissue sample and found a significant increase in BH4 in the heart and kidney as well as higher BH4 levels by trend in the brain of septic rats compared to control rats. These findings correspond to reports on augmented nitric oxide and BH4 levels in both animals and patients with septic shock.

Intraocular Pressure-Induced Endothelial Dysfunction of Retinal Blood Vessels Is Persistent, but Does Not Trigger Retinal Ganglion Cell Loss

Abstract: Research has been conducted into vascular abnormalities in the pathogenesis of glaucoma, but conclusions remain controversial. Our aim was to test the hypothesis that retinal endothelial dysfunction induced by elevated intraocular pressure (IOP) persists after IOP normalization, further triggering retinal ganglion cell (RGC) loss. High intraocular pressure (HP) was induced in mice by episcleral vein occlusion (EVO). Retinal vascular function was measured via video microscopy in vitro. The IOP, RGC and their axons survival, levels of oxidative stress and inflammation as well as vascular pericytes coverage, were determined. EVO caused HP for two weeks, which returned to baseline afterwards. Mice with HP exhibited endothelial dysfunction in retinal arterioles, reduced density of RGC and their axons, and loss of pericytes in retinal arterioles. Notably, these values were similar to those of mice with recovered IOP (RP). Levels of oxidative stress and inflammation were increased in HP mice but went back to normal in the RP mice. Our data demonstrate that HP induces persistent endothelial dysfunction in retinal arterioles, which persists one month after RP. Oxidative stress, inflammation, and loss of pericytes appear to be involved in triggering vascular functional deficits. Our data also suggest that retinal endothelial dysfunction does not affect RGC and their axon survival.

The Involvement of Sirtuin 1 Dysfunction in High-Fat Diet-Induced Vascular Dysfunction in Mice

Abstract: High-fat diet (HFD)-induced vascular impairment in mice is associated with a dysfunction of the perivascular adipose tissue (PVAT). The present study was conducted to investigate the involvement of sirtuin 1 (SIRT1). Male C57BL/6J mice were fed an HFD for 20 weeks to induce obesity. Vascular function was analyzed using a wire myograph system. In obese mice, the vasodilator response of PVAT-containing aortas to acetylcholine was reduced, although the vascular function of PVAT-free aortas remained normal. SIRT1 activity in PVAT of obese mice was reduced despite enhanced SIRT1 expression. Nicotinamide adenine dinucleotide (NAD+) levels and the NAD+/NADH ratio in the PVAT of obese mice were decreased, which was likely attributable to a downregulation of the NAD+-producing enzyme NAMPT. The reduced SIRT1 activity was associated with an enhanced acetylation of the endothelial nitric oxide synthase (eNOS) in the PVAT. Ex vivo incubation of PVAT-containing aorta from obese mice with NAD+ led to a complete normalization of vascular function. Thus, reduced SIRT1 activity due to NAD+ deficiency is involved in obesity-induced PVAT dysfunction.

Analysis of 16 studies in nine rodent models does not support the hypothesis that diabetic polyuria is a main reason of urinary bladder enlargement

Abstract: The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin-injected rats, which may contribute to the frequent diabetic uropathy. Much less data exists for models of type 2 diabetes. Diabetic polyuria has been proposed as the pathophysiological mechanism behind bladder enlargement. Therefore, we explored such a relationship across nine distinct rodent models of diabetes including seven models of type 2 diabetes/obesity by collecting data on bladder weight and blood glucose from 16 studies with 2–8 arms each; some studies included arms with various diets and/or pharmacological treatments. Data were analysed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargement in streptozotocin rats and minor if any enlargement in fructose-fed rats, db/db mice and mice on a high-fat diet; enlargement was present in some of five not reported previously models. Bladder weight was correlated with blood glucose as a proxy for diabetic polyuria within some but not other models, but correlations were moderate to weak except for RIP-LCMV mice (r 2 of pooled data from all studies 0.0621). Insulin levels also failed to correlate to a meaningful extent. Various diets and medications (elafibranor, empagliflozin, linagliptin, semaglutide) had heterogeneous effects on bladder weight that often did not match their effects on glucose levels. We conclude that the presence and extent of bladder enlargement vary markedly across diabetes models, particularly type 2 diabetes models; our data do not support the idea that bladder enlargement is primarily driven by glucose levels/glucosuria.

Insulin is Not Driving Urinary Bladder Enlargement in Rodent Models of Diabetes

Abstract: The urinary bladder is enlarged in all models of type 1 and several of type 2 diabetes (doi 10.1002/nau.23786). We have previously reported that such enlargement is correlated to insulin, but not glucose levels in fructose‐fed rats (doi 10.1096/fasebj.2020.34.s1.00542). Because this was surprising, we have now repeated that study and expanded our analysis to other models of diabetes and obesity.

Cases Abusing Brain Death Definition in Organ Procurement in China

Abstract: Abstract Organ donation after brain death has been practiced in China since 2003 in the absence of brain death legislation. Similar to international standards, China’s brain death diagnostic criteria include coma, absence of brainstem reflexes, and the lack of spontaneous respiration. The Chinese criteria require that the lack of spontaneous respiration must be verified with an apnea test by disconnecting the ventilator for 8 min to provoke spontaneous respiration. However, we have found publications in Chinese medical journals, in which the donors were declared to be brain dead, yet without an apnea test. The organ procurement procedures started with initiating “intratracheal intubation for mechanical ventilation after brain death,” indicating that a brain death diagnosis was not performed. The purpose of the intubation was not to resuscitate the patient but rather was directly related to facilitating the explantation of organs. Moreover, it was unmistakably stated in two of these publications that the cardiac arrest was induced in these patients without brain death determination by cold St. Thomas cardioplegic solution or other cold myocardial protection solutions. This means that the condition of these donors neither met the criteria of brain death nor that of cardiac death. In other words, the “donor organs” may well have been procured in these cases from living human beings. Thus, brain death definition is abused in China by some individuals for organ harvesting, and a systematic investigation is needed to clarify the situation of organ donation after brain death in China.